Derivatives of procaspase-activating compound 1 (PAC-1) and their anticancer activities

Howard S. Roth, Paul J. Hergenrother

Research output: Contribution to journalArticlepeer-review


PAC-1 induces the activation of procaspase-3 in vitro and in cell culture by chelation of inhibitory labile zinc ions via its ortho-hydroxy-N-acylhydrazone moiety. First reported in 2006, PAC-1 has shown promise in cell culture and animal models of cancer, and a Phase I clinical trial in cancer patients began in March 2015 (NCT02355535). Because of the considerable interest in this compound and a well-defined structure-activity relationship, over 1000 PAC-1 derivatives have been synthesized in an effort to vary pharmacological properties such as potency and pharmacokinetics. This article provides a comprehensive examination of all PAC-1 derivatives reported to date. A survey of PAC-1 derivative libraries is provided, with an indepth discussion of four derivatives on which extensive studies have been performed.

Original languageEnglish (US)
Pages (from-to)201-241
Number of pages41
JournalCurrent Medicinal Chemistry
Issue number3
StatePublished - Jan 1 2016


  • Apoptosis
  • Cancer
  • Library
  • PAC-1
  • Procaspase-3
  • Zinc

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Medicine
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry


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